Science you should know

The neuroscience of the Neanderthal

Earlier this year Prospect science writer Philip Ball had his own “mini-brain” grown in a laboratory. Researchers now plan to put the method to different use, and in doing so learn more about an extinct close relative

Philip Ball’s “mini brain,” stained with fluorescent dye to show the neurons. Photo: Chris Lovejoy and Selina Wray, UCL Plans to grown Neanderthal “mini-brains” take this already science-fictional biomedical technology to new extremes. Mini-brains are a form of organoids—tiny organ-like clusters of cells grown in the laboratory, both for fundamental research in biology and also for possible transplantation to replace damaged or malfunctioning organs. But the new proposal, by eminent palaeontologist Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, would use the technique to investigate our extinct close relatives the Neanderthals, attempting to figure out what if anything made their brains different from those of the early Homo sapiens with whom they coexisted. It’s a bold idea, and indeed some researchers see it as a long shot that might tell us rather little. But at the very least it shows how advances in genetics, tissue engineering and stem-cell technology, and palaeontology could converge to let us address questions one might have imagined long lost in the mists of time. Mini-brains are formed when stem cells—either made by “induced” means from adult body cells or taken from human embryos—are coaxed into becoming neurons, the nerve cells that signal to each other in the brain. These stem cells are capable of growing into any tissue in the body, and in a cell culture (where they are sustained in a medium that supplies essential nutrients) they can be guided into particular tissue types—heart, kidney or muscle cells, say—typically by adding the right cocktail of proteins to the medium. But in general, these cultured stem cells don’t just proliferate into a vague mass of the target cell type. Instead they develop some of the organisation found in real organs—an indication that cells are already programmed with the instructions needed for building the complex structures and organs of the body. So it is for neurons grown from cultured stem cells: they develop into brain-like structures, for example making layers of neurons like those seen in the cortex. The resulting brain organoids can grow to the size of a small pea before cells in the interior start to die for lack of a blood supply. The organoid is far from a miniature version of a real brain, but it reproduces enough of the developing brain’s structure to provide researchers with a decent model of that growth process in a fetus. I’m no stranger to mini-brains, having had one of my “own” grown earlier this year (see Prospect’s April issue). That was an offshoot of a project on perceptions and care of dementia funded by the Wellcome Trust, and the researchers who grew a mini-brain from cells taken from my arm and converted into a stem-cell-like state are seeking to understand the genetics behind Alzheimer’s and other neurodegenerative conditions. Seeking to understand the neuroscience of Neanderthals is a challenge of a different order. These creatures were a form of humans who lived between about 250,000 and 40,000 years ago. They were close enough to us that interbreeding was possible, which is why people not of African descent typically have a few percent of Neanderthal genes in their genomes. Pääbo’s lab sequenced the Neanderthal genome, patched together from the fossil remains of several individuals, in 2010. Among the differences with the genomes of modern humans, the researchers found distinctively Neanderthal variants in a few genes linked to brain development. How, and how much, did those genes make Neanderthal brains different from ours? We now know that the stereotype of Neanderthals as slow and more “primitive” is wrong: these people had a rather sophisticated culture that included art and probably ritual, and their brains were in fact bigger than ours (although that doesn’t itself imply “smarter”). The reasons why Neanderthals became extinct are not clear—it’s possible that some cognitive ability of modern humans gave them the edge, but equally the reasons might lie elsewhere, for example in a greater susceptibility to some diseases. Pääbo hopes to get some clues by using gene-editing methods to transfer some of the Neanderthal genes into human stem cells and growing them into mini-brains. This won’t by any means result in “Neanderthal mini-brains,” but it could show whether those genes alter the development of brains in ways that could be seen in the shapes and structures of the organoids, and which might at least hint at reasons for cognitive differences. To do this, the researchers will use the technique known as Crispr, revealed around 2012-3 as a means for allowing our gene-carrying DNA to be edited very precisely. The method will enable selected modern human genes to be rewritten in their “Neanderthal” form. But what are the prospects of learning anything this way? Madeline Lancaster of Cambridge University, one of the pioneers of growing brain organoids, says “my guess is that you wouldn’t see any differences.” But still, she adds, “it’ll be interesting to see what “neanderthalised” brain organoids look like.” Even an observation of no difference, Lancaster says, would be interesting, because it would argue against there being some gross difference in brain structure that compromised the Neanderthals. Equally, though, any observed differences might be hard to interpret, just as they generally are when comparing brain organoids of different species. That’s especially so when there are no fully grown Neanderthal brains to compare against, so as to be sure that any observed differences are real. The dream result—though frankly don’t get your hopes up—could be finding that “neanderthalised” brains do seem to grown differently in ways suggesting not so much that they thought less adeptly than us, but rather that they had a different behavioural and conceptual repertoire.

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